Hydrogel-Encapsulated Beads Enable Proximity-Driven Encoded Library Synthesis and Screening

نویسندگان

چکیده

Encoded combinatorial library technologies have dramatically expanded the chemical space for screening but are usually only analyzed by affinity selection binding. It would be highly advantageous to reformat outputs ”one-bead-one-compound” solid-phase libraries, unlocking activity-based and cellular capabilities. Here, we describe hydrogel-encapsulated magnetic beads that enable such a transformation. Bulk emulsion polymerization of polyacrylamide hydrogel shells around microbeads yielded uniform particles (7 ± 2 μm diameter) compatible with diverse in-gel functionalization (amine, alkyne, oligonucleotides) transformations associated DNA-encoded synthesis (acylation, enzymatic DNA ligation). In case study reformatting mRNA display transcription from DNA-templated encapsulated in gel colocalized both RNA via hybridization copolymerized complementary translation puromycin labeling. Two control epitope templates (V5, HA) were successfully enriched (50- 99-fold, respectively) an NNK5 bead screen FACS. Proximity-driven concert sample manipulation provides plausible means encoded libraries at scale.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Generation and screening of an oligonucleotide-encoded synthetic peptide library.

We have prepared a library of approximately 10(6) different peptide sequences on small, spherical (10-microns diameter) beads by the combinatorial chemical coupling of both L- and D-amino acid building blocks. To each bead is covalently attached many copies of a single peptide sequence and, additionally, copies of a unique single-stranded oligonucleotide that codes for that peptide sequence. Th...

متن کامل

Fabrication of a microfluidic device for studying the in situ drug-loading/release behavior of graphene oxide-encapsulated hydrogel beads

Background Controlled drug delivery system is highly important for not only prolonged the efficacy of drug but also cellular development for tissue engineering. A number of biopolymer composites and nanostructured carriers behave been used for the controlled drug delivery of therapeutics. Recently, in vitro microfluidic devices that mimic the human body have been developed for drug-delivery app...

متن کامل

DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis

The promise of exploiting combinatorial synthesis for small molecule discovery remains unfulfilled due primarily to the "structure elucidation problem": the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffol...

متن کامل

Parallel synthesis and antimalarial screening of a 4-aminoquinoline library.

Due to growing problems with drug resistance, there is an outstanding need for new, cost-effective drugs for the treatment of malaria. The 4-aminoquinolines have provided a number of useful antimalarials, and Plasmodium falciparum, the causative organism for the most deadly form of human malaria, is generally slow to develop resistance to these drugs. Therefore, diverse screening libraries of q...

متن کامل

Photo- and electropatterning of hydrogel-encapsulated living cell arrays.

Living cells have the potential to serve as sensors, naturally integrating the response to stimuli to generate predictions about cell fate (e.g., differentiation, migration, proliferation, apoptosis). Miniaturized arrays of living cells further offer the capability to interrogate many cells in parallel and thereby enable high-throughput and/or combinatorial assays. However, the interface betwee...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: ACS central science

سال: 2023

ISSN: ['2374-7951', '2374-7943']

DOI: https://doi.org/10.1021/acscentsci.3c00316